Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player le...Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are considered the most common mesenchymal tumors of the gastrointestinal tract.Microvessel density(MVD)constitutes a direct method of vascularity quantification and ha...BACKGROUND Gastrointestinal stromal tumors(GISTs)are considered the most common mesenchymal tumors of the gastrointestinal tract.Microvessel density(MVD)constitutes a direct method of vascularity quantification and has been associated with survival rates in multiple malignancies.AIM To appraise the effect of MVD on the survival of patients with GIST.METHODS This study adhered to Systematic reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.Electronic scholar databases and grey literature repositories were systematically screened.The Fixed Effects or Random Effects models were used according to the Cochran Q test.RESULTS In total,6 eligible studies were identified.The pooled hazard ratio(HR)for disease free survival(DFS)was 8.52(95%CI:1.69-42.84,P=0.009).The odds ratios of disease-free survival between high and low MVD groups at 12 and 60 mo did not reach statistical significance.Significant superiority of the low MVD group in terms of DFS was documented at 36 and 120 mo(OR:8.46,P<0.0001 and OR:22.71,P=0.0003,respectively)as well as at metastases rate(OR:0.11,P=0.0003).CONCLUSION MVD significantly correlates with the HR of DFS and overall survival rates at 36 and 120 mo.Further prospective studies of higher methodological quality are required.展开更多
BACKGROUND Microvessel density(MVD)has been proposed as a direct quantification method of tumor neovascularization.However,the current literature regarding the role of MVD in differentiated thyroid carcinoma(DTC)remai...BACKGROUND Microvessel density(MVD)has been proposed as a direct quantification method of tumor neovascularization.However,the current literature regarding the role of MVD in differentiated thyroid carcinoma(DTC)remains inconclusive.AIM To appraise the effect of tumoral MVD on the survival of patients with DTC.METHODS This meta-analysis was based on the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.The electronic databases Medline,Web of Science,and Scopus were systematically screened.A fixedeffects or random-effects model was used,according to the Cochran Q test.The data were then extracted and assessed on the basis of the Reference Citation Analysis(https://www.referencecitationanalysis.com/).RESULTS A total of nine studies were included in the present study.Superiority of low MVD tumors in terms of 10-year disease free survival(OR:0.21,95%CI:0.08–0.53)was recorded.Lowly vascularized thyroid cancers had a lower recurrence rate(OR:13.66,95%CI:3.03–61.48).Moreover,relapsing tumors[weighed mean difference(WMD):11.92,95%CI:6.32–17.52]or malignancies with regional lymph node involvement(WMD:8.53,95%CI:0.04–17.02)presented with higher tumoral MVD values.CONCLUSION MVD significantly correlates with the survival outcomes of thyroid cancer patients.However,considering several study limitations,further prospective studies of higher methodological and quality level are required.展开更多
文摘Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are considered the most common mesenchymal tumors of the gastrointestinal tract.Microvessel density(MVD)constitutes a direct method of vascularity quantification and has been associated with survival rates in multiple malignancies.AIM To appraise the effect of MVD on the survival of patients with GIST.METHODS This study adhered to Systematic reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.Electronic scholar databases and grey literature repositories were systematically screened.The Fixed Effects or Random Effects models were used according to the Cochran Q test.RESULTS In total,6 eligible studies were identified.The pooled hazard ratio(HR)for disease free survival(DFS)was 8.52(95%CI:1.69-42.84,P=0.009).The odds ratios of disease-free survival between high and low MVD groups at 12 and 60 mo did not reach statistical significance.Significant superiority of the low MVD group in terms of DFS was documented at 36 and 120 mo(OR:8.46,P<0.0001 and OR:22.71,P=0.0003,respectively)as well as at metastases rate(OR:0.11,P=0.0003).CONCLUSION MVD significantly correlates with the HR of DFS and overall survival rates at 36 and 120 mo.Further prospective studies of higher methodological quality are required.
文摘BACKGROUND Microvessel density(MVD)has been proposed as a direct quantification method of tumor neovascularization.However,the current literature regarding the role of MVD in differentiated thyroid carcinoma(DTC)remains inconclusive.AIM To appraise the effect of tumoral MVD on the survival of patients with DTC.METHODS This meta-analysis was based on the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.The electronic databases Medline,Web of Science,and Scopus were systematically screened.A fixedeffects or random-effects model was used,according to the Cochran Q test.The data were then extracted and assessed on the basis of the Reference Citation Analysis(https://www.referencecitationanalysis.com/).RESULTS A total of nine studies were included in the present study.Superiority of low MVD tumors in terms of 10-year disease free survival(OR:0.21,95%CI:0.08–0.53)was recorded.Lowly vascularized thyroid cancers had a lower recurrence rate(OR:13.66,95%CI:3.03–61.48).Moreover,relapsing tumors[weighed mean difference(WMD):11.92,95%CI:6.32–17.52]or malignancies with regional lymph node involvement(WMD:8.53,95%CI:0.04–17.02)presented with higher tumoral MVD values.CONCLUSION MVD significantly correlates with the survival outcomes of thyroid cancer patients.However,considering several study limitations,further prospective studies of higher methodological and quality level are required.
